Safety and Activity of SNX-5422 Plus Ibrutinib in CLL

NCT02914327 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: SNX-5422-CLN1-011
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will result in the removal of mutated BTK from blood mononuclear cells and/or prevents or delays disease progression of subjects with CLL

Conditions

Cancer

Keywords

CLL; Leukemia, Chronic Lymphocytic; Hsp90; BTK; Ibrutinib

Outcome Measures

Primary Outcomes (1)

• Efficacy of the combination of SNX-5422 and ibrutinib

  Change in percent of mutated BTK in CLL cells

  Every 12 weeks up to 52 weeks

Secondary Outcomes (4)

• Number of subjects reporting adverse events

  Day 28 of each 4 week cycle from randomization up to 52 weeks

• Time to disease progression

  Up to 52 weeks

• Clinical Laboratory testing

  Day 28 of each 4 week cycle from randomization up to 52 weeks

• Electrocardiogram

  Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks

Study Arms (1)

SNX-5422 plus ibrutinib

EXPERIMENTAL

Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle. Subjects will repeat the 28-day schedule until the cancer progresses or the subject is unable to tolerate the therapy

Drug: SNX-5422 plus ibrutinib

Interventions

SNX-5422 plus ibrutinib DRUG

SNX-5422 capsule(s) dosed every other day for 21 days out of a 28-day treatment cycle to a total dose of 56 mg/m2 SNX-5422. Subjects will self-administer daily oral ibrutinib in the afternoon at least 8 hours apart from SNX-5422 for 28 days of each cycle.

Also known as: Imbruvica

SNX-5422 plus ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
• A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.
• No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
• Presence of mutated BTK in ≥ 4% of peripheral blood or bone marrow CLL cells, or ≥1% and rising on two separate measurements obtained at least 28 days apart.
• Life expectancy of at least 9 months
• Karnofsky performance score 70
• Adequate baseline laboratory assessments
• Signed informed consent form
• Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia
• Subjects with reproductive capability must agree to practice adequate contraception methods.

You may not qualify if:

• Subjects experiencing toxicity with ibrutinib
• Prior treatment with any Hsp90 inhibitor.
• Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
• Conventional chemotherapy or radiation within 4 weeks.
• The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
• Screening ECG QTc interval 470 msec for females, 450 msec for males.
• At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
• Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
• Gastrointestinal diseases or conditions that could affect drug absorption
• Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• History of documented adrenal dysfunction not due to malignancy.
• History of chronic liver disease.
• Active hepatitis A or B.
• Current alcohol dependence or drug abuse.
• Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose

Sponsors & Collaborators

• Esanex Inc.: lead

Study Sites (1)

Wexner Medical Center, Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

SNX-5422; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 26, 2016
• Study Start: February 2, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: July 30, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)